Design at the atomic level: design of biaryloxazolidinones as potent orally active antibiotics.
We have developed a first generation of hybrid sparsomycin-linezolid compounds into a new family of orally bioavailable biaryloxazolidinones that have activity against both linezolid-susceptible and -resistant gram-positive bacteria as well as the fastidious gram-negative bacteria Haemophilus influenzae and Moraxella catarrahalis. The convergent synthesis of these new compounds is detailed.
Zhou
Jiacheng
J
Department of Medicinal Chemistry, Rib-X Pharmaceuticals Inc., 300 George Street, Suite 301, New Haven, CT 06511, USA.
Bhattacharjee
Ashoke
A
Chen
Shili
S
Chen
Yi
Y
Duffy
Erin
E
Farmer
Jay
J
Goldberg
Joel
J
Hanselmann
Roger
R
Ippolito
Joseph A
JA
Lou
Rongliang
R
Orbin
Alia
A
Oyelere
Ayomi
A
Salvino
Joe
J
Springer
Dane
D
Tran
Jennifer
J
Wang
Deping
D
Wu
Yusheng
Y
Johnson
Graham
G
D000081:Acetamides / Q000494:pharmacology; D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006193:Haemophilus influenzae / Q000187:drug effects; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D001936:Moraxella catarrhalis / Q000187:drug effects; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013033:Sparsomycin / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D013033:Sparsomycin; D000069349:Linezolid